2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 5-Bromo-2-chloro-4-(5-chlorothiophen-2-yl)pyrimidine

Temperature

-10 °C

A solution of 2-chlorothiophene (0.467 mL, 5 mmol) in anhydrous tetrahydrofuran (5 mL) with treated with a solution of lithium diisopropylamide (2 M in THF, 2.75 mL, 5.5 mmol) at −40° C. under a nitrogen atmosphere. After 15 min, the reaction was allowed to warm up to −10° C. and held at that temperature for 20 min. The reaction was then cooled back down to −40° C. and 5-bromo-2-chloropyrimidine (1.06 g, 5.5 mmol), dissolved in anhydrous THF (10 mL) was added to the reaction slowly. After 2 h, a mixture of 1:1 methanol/acetic acid (2 mL) was added to the reaction. After 15 min, a solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (1.36 g, 6 mmol) in 10 mL of THF was added. The reaction was stirred for an additional 15 min and then the cooling bath was removed. The mixture was stirred for 1 h and then cooled to 0° C. with an ice bath. 5 N sodium hydroxide (5 mL) was added to the reaction mixture which was stirred for an additional 5 min. The reaction was then diluted with ethyl acetate (20 mL) and water (20 mL). The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine. The organic layer was then dried with sodium sulfate, concentrated and purified by flash chromatography using a gradient of 5 to 20% ethyl acetate in hexanes to obtain a yellow solid. Yield=0.6 g. MS (M+H)+ 311/313.

1. waitheld at that temperature for 20 min
2. additionwas added to the reaction slowly
3. waitAfter 2 h
4. additionwas added to the reaction
5. waitAfter 15 min
6. customthe cooling bath was removed
7. stirringThe mixture was stirred for 1 h
8. temperaturecooled to 0° C. with an ice bath
9. addition5 N sodium hydroxide (5 mL) was added to the reaction mixture which
10. stirringwas stirred for an additional 5 min
11. additionThe reaction was then diluted with ethyl acetate (20 mL) and water (20 mL)
12. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water and brine
13. dry with materialThe organic layer was then dried with sodium sulfate
14. concentrationconcentrated
15. custompurified by flash chromatography
16. customto obtain a yellow solid

ORD record

ord-7b8549a03e23483fbdfb5074120c5fa9

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07858785B2